Figure 2.

Potential mechanisms whereby SGLT2i may promote ketosis and increase the risk of ketoacidosis in T1D patients. SGLT2i decrease glucose by an insulin-independent mechanism. To minimize the risk of hypoglycemia, T1D patients may need to decrease their insulin dose, which is predicted to increase the rate of adipose tissue lipolysis, free fatty acid release, and hepatic ketogenesis. In addition, SGLT2i have been demonstrated to increase plasma glucagon levels in T2D patients possibly to compensate for increased urinary excretion of glucose. SGLT2i also reduce renal tubular sodium and glucose reabsorption and increase the reabsorption of ketoacids, resulting in decreased renal clearance of ketone bodies. Figure reproduced from Taylor et al. ²⁴

Abbreviations: SGLT2i, sodium-glucose cotransporter-2 inhibitors; T1D, type 1 diabetes; T2D, type 2 diabetes.